Human gastric mucosal adenylate cyclase activity: effects of various cytoprotective prostaglandins.
Several prostaglandins prevent ulcer formation (called cytoprotection) by a mechanism other than inhibition of gastric acid secretion. One suggestion is that they increase cyclic AMP in non-parietal cells. A variety of prostaglandins with potent cytoprotective properties were tested for their capacity to modulate adenylate cyclase activity in homogenates of human gastric mucosa. Prostaglandin E2, prostacyclin (PGI2) and 15(S)-methyl-PGE2 stimulated the cyclase in human gastric mucosal biopsy specimens in a dose-dependent manner. Cytoprotective prostaglandins without antisecretory properties such as PGF2 beta were also able to activate the enzyme system dose-dependently. In contrast, cytoprotective prostaglandins such as PGD2, the PGE1-analogue, SC-29333, and the prostaglandin-like compound C83 did not stimulate human gastric adenylate cyclase. Whereas PGD2 did not modulate enzyme activity at all, SC-29333 and C83, at concentrations greater than 10 mumol/l, inhibited basal and PGE2-stimulated enzyme activities. These studies suggest that cyclic AMP is not directly related to the cytoprotective effect of prostaglandins, at least in human gastric mucosa.
D000262:Adenylyl Cyclases / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D011453:Prostaglandins / Q000494:pharmacology*
D011453:Prostaglandins; D006160:Guanosine Triphosphate; D000262:Adenylyl Cyclases